PEG-PCL and PEG-PLA from PolySciTech used to understand protein – block copolymer micelle interactions

 

Block copolymers (PEG-PLGA, PEG-PCL, PEG-PLA, etc.) are commonly used to create drug-delivery platforms as they self-form into micelles which can entrap and carry hydrophobic drugs. Like all chemicals, these structures have a complex interaction with the multitude of components present in human blood which leads to their eventual disruption however exactly 'how' this happens is not well known. Recently, researchers at University of Illinois, Chicago used PEG-PCL (cat# AK073) and PEG-PLA (cat# AK009) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create micelles and investigated their interactions with serum albumins. This research holds promise to provide fundamental understanding to aid in the further development of micelle-based delivery systems. Read more: Dial, Catherine F., and Richard A. Gemeinhart. "Biophysical Characterization of Interactions between Serum Albumin and Block Copolymer Micelles." ACS Biomaterials Science & Engineering (2022). https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.2c00016

“Block copolymer micelles have demonstrated great promise in the solubilization of hydrophobic drugs, but an understanding of the blood stability of the drug-laden micelles is needed for therapeutic advancement of micelle technologies. Following intravenous administration, mPEG-CL and mPEG-LA micelles have demonstrated quick release of their cargo and disassembly in blood, but the prevailing mechanisms of micelle disruption and key biomacromolecules driving this disruption have yet to be elucidated. Although protein interactions with solid polymeric nanoparticles have been characterized, not much is known regarding protein interactions with dynamic block copolymer micelles. Herein, we characterize the interaction of bovine and human serum albumins (BSA and HSA) with polymeric micelles, mPEG-CL and mPEG-LA, using protein fluorescence, isothermal titration calorimetry (ITC), and circular dichroism (CD) spectroscopy. We find that BSA and HSA have interactions with mPEG-CL, while only HSA is observed to weakly interact with mPEG-LA. Protein fluorescence suggests that binding of HSA to mPEG-CL and mPEG-LA is driven by electrostatic interactions. ITC suggests an interaction between serum albumin and mPEG-CL block copolymers driven by hydrogen bonding and electrostatic interactions in physiological MOPS-buffered saline, while mPEG-LA has no measurable interaction with either of the serum albumins. CD spectroscopy demonstrates that the protein secondary structure is intact in both proteins in the presence of mPEG-CL and mPEG-LA. Overall, BSA is not always predictive of polymeric interactions with HSA. Understanding of interactions between serum proteins and block copolymer micelles and the exact mechanisms of destabilization will direct the rational design of block copolymer systems for improving blood stability. KEYWORDS: micelle polymer albumin interactions protein−polymer interactions”